Molecules 2018, 23, 761
9 of 13
N-(2-(2-(2-(4-Hydroxybenzylidene)-hydrazinyl)-2-oxoethylamino)-2-oxoethyl)-nicotinamide (
6
): Yield: 62%;
◦
melting point: 280–281 C, IR (cm−1): (KBr):
ν
= 3420 (OH), 3200 (NH stretching), 2951 (CH, aromatic),
1
2839 (CH, aliphatic), 1645, 1593, and 1558 (C=O amide I, II, and III, respectively). H-NMR (500 MHz,
δ
, ppm, DMSO-d6): δ = 9.15 (s, 1H, OH, D2O exchangeable, aromatic C–OH), 9.12, 9.00 (s, 2H, 2NH,
D2O exchangeable, NHCH2CONHN=CH–Phe, amide), 8.98 (1H, aromatic H, C1, Pyr.), 8.62 (1H,
aromatic H, C5, Pyr.), 8.55 (1H, aromatic H, C3, Pyr.), 8.39 (s, 1H, 1NH, D2O exchangeable, Py–CONH
amide), 8.18–8.16 (d, 1H, N=CH–Phe), 8.08 (1H, aromatic H, C4, Pyr.), 7.55–7.40 (4H, the remaining
aromatic H), 2.96–2.93 (t, 4H, 2CH2,
α
-gly). 13C-NMR (125 MHz,
δ, ppm, DMSO-d6):
δ
= 173–170
(3CO), 160–122 (11aromatic C), 140.5 (N=CH, Hydrazide), 41.5–40.0 (aliphatic C, 2CH2,
α
-gly). MS (EI,
70 eV): m/z (%) = 356 (M+ + 1, 7.55), 355 (M+, 11.05), 224 (6.70), 155 (6.15), 68 (11.14), 56 (100), 50 (14.49).
Molecular formula (molecular weight): C17H17N5O4 (355.3). Calculated analysis: C, 57.46; H, 4.82;
N, 19.71; found: C, 57.45; H, 4.84; N, 19.75.
The general procedure for the synthesis of Compounds 7 and 8: A mixture of Compound 4 (0.01 mol), phenyl
isocyanate, and/or methyl isothiocyanate (0.01 mol) and triethyl amine as a catalytic amount in dry
benzene (20 mL) was refluxed for 7 h. The mixture was thereafter concentrated. The precipitated was
filtered off and recrystallized from ethanol to give the new Compounds 7 and 8.
N-(2-(2-(2-(Methylcarbamothioyl)-hydrazinyl)-2-oxoethylamino)-2-oxoethyl)-nicotinamide (7): Yield: 77%;
◦
melting point: 202–204 C, IR (cm−1): (KBr):
ν
= 3425 (NH stretching), 3251 (CH, aromatic), 3143 (CH,
1
aliphatic), 1590, 1542, and 1515 (C=O amide I, II, and III, respectively). H-NMR (500 MHz,
δ, ppm,
DMSO-d6):
8.60 (1H, aromatic H, C5, Pyr.), 8.45, 7.80 (2H, aromatic H, C3 and C4, Pyr.), 3.50–3.42 (t, 4H, 2CH2,
-gly), 2.00 (s, 3H, CH3,). 13C-NMR (125MHz,
, ppm, DMSO-d6): = 183 (CS), 165 (3CO), 145–140
(5 aromatic C), 45.7 (aliphatic C, 2CH2, -gly), 31.1 (aliphatic C, CH3). MS (EI, 70 eV): m/z (%) = 325
δ = 9.50–8.90 (5s, 5H, 5NH, D2O exchangeable, amide), 8.75 (1H, aromatic H, C1, Pyr.),
α
δ
δ
α
(M+ + 1, 57.45), 324 (M+, 63.30), 299 (60.64), 199 (100), 144 (47.87), 75 (57.45), 65 (81.91), 51 (46.28).
Molecular formula (molecular weight): C12H16N6O3S (324.4). Calculated analysis: C, 44.43; H, 4.97; N,
25.91; S, 9.89; found: C, 44.44; H, 5.00; N, 25.95; S, 9.86.
N-(2-oxo-2-(2-oxo-2-(2-(◦Phenylcarbamoyl)-hydrazinyl)-ethylamino)-ethyl)-nicotinamide (
8): Yield: 55%;
= 3290 (NH stretching), 3056 (CH, aromatic), 2677 (CH,
melting point: 230–231 C, IR (cm−1): (KBr):
ν
1
aliphatic), 1688, 1660, 1630 and 1599 (C=O amide I, II, III, and IV, respectively). H-NMR (500 MHz,
δ
, ppm, DMSO-d6):
Pyr.), 8.51 (1H, aromatic H, C5, Pyr.), 8.39 (1H, aromatic H, C3, Pyr.), 7.62–6.93 (6H, the remaining
aromatic H), 3.83–3.66 (t, 4H, 2CH2,
-gly). MS (EI, 70 eV): m/z (%) = 371 (M+ + 1, 1.77), 370 (M+, 2.79),
δ = 9.22–8.85 (5s, 5H, 5NH, D2O exchangeable, amide), 8.80 (1H, aromatic H, C1,
α
322 (100), 236 (4.24), 91 (12.08), 77 (17.96), 64 (43.17), 50 (10.19). Molecular formula (molecular weight):
C17H18N6O4 (370.4). Calculated analysis: C, 55.13; H, 4.90; N, 22.69; found: C, 55.15; H, 4.94; N, 22.73.
The general procedure for the synthesis of Compounds
9 and 10: A mixture of Compound 7 or 8 (0.01 mol)
in ethanol (30 mL) and chloroacetic acid (0.01 mol) was refluxed for 10 h. The reaction mixture was
concentrated. The precipitate was filtered off and recrystallized from the ethanol to give the corresponding
candidates (9,10), respectively.
N-(2-(2-(2-(Methylimino)-4-oxothiazolidin-3-ylamino)-2-oxoethylamino)-2-oxoethylamino)-2-oxoethyl)
nicotinamide (
2981 (CH, aromatic), 2943 (CH, aliphatic), 1616, 1603 and 1524 (C=O amide I, II and III, respectively).
1H-NMR (500 MHz,
, ppm, DMSO-d6): = 9.40–9.21 (3s, 3H, 3NH, D2O exchangeable, amide),
9 ν = 3429 (NH stretching),
): Yield: 70%; melting point: 151–153 ◦C, IR (cm−1): (KBr):
δ
δ
8.72–8.24 (m, 4H, aromatic H, Pyr.), 4.45 (t, 2H, CH2, oxazolidine ring), 3.17, 2.95 (t, 4H, 2CH2, α-gly),
1.34–1.10 (s, 3H, CH3). MS (EI, 70 eV): m/z (%) = 365 (M+ + 1, 2.37), 364 (M+, 6.11), 258 (24.53), 73 (100),
57 (25.80), 50 (2.08). Molecular formula (molecular weight): C14H16N6O4S (364.4). Calculated analysis:
C, 46.15; H, 4.43; N, 23.06; S, 8.80; found: C, 46.17; H, 4.45; N, 23.03; S, 8.85.
N-(2-oxo-2-(2-oxo-2-(4-oxo-2-(Phenylimino)-oxazolidin-3-ylamino)-ethylamino)-ethyl)-nicotinamide
(
10):
◦
Yield: 80%; melting point: 98–100 C, IR (cm−1): (KBr):
ν = 3431 (NH stretching), 3295 (CH, aromatic),